Research Article: Predictors of long-term cognitive outcome in Alzheimer’s disease

Date Published: July 20, 2011

Publisher: BioMed Central

Author(s): Carina Wattmo, Åsa K Wallin, Elisabet Londos, Lennart Minthon.


The objective of this study was to describe the longitudinal cognitive outcome in Alzheimer’s disease (AD) and analyze factors that affect the outcome, including the impact of different cholinesterase inhibitors (ChEI).

In an open, three-year, nonrandomized, prospective, multicenter study, 843 patients were treated with donepezil, rivastigmine, or galantamine in a routine clinical setting. At baseline and every six months, patients were assessed using several rating scales, including the Mini-Mental State Examination (MMSE) and the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) and the dose of ChEI was recorded. Sociodemographic and clinical characteristics were investigated. The relationships of these predictors with longitudinal cognitive ability were analyzed using mixed-effects models.

Slower long-term cognitive decline was associated with a higher cognitive ability at baseline or a lower level of education. The improvement in cognitive response after six months of ChEI therapy and a more positive longitudinal outcome were related to a higher mean dose of ChEI, nonsteroidal anti-inflammatory drug (NSAID)/acetylsalicylic acid usage, male gender, older age, and absence of the apolipoprotein E (APOE) ε4 allele. More severe cognitive impairment at baseline also predicted an improved response to ChEI treatment after six months. The type of ChEI agent did not influence the short-term response or the long-term outcome.

In this three-year AD study performed in a routine clinical practice, the response to ChEI treatment and longitudinal cognitive outcome were better in males, older individuals, non-carriers of the APOE ε4 allele, patients treated with NSAIDs/acetylsalicylic acid, and those receiving a higher dose of ChEI, regardless of the drug agent.

Partial Text

Alzheimer’s disease (AD) is the most prevalent cause of dementia among the elderly, accounting for 50% to 60% of cases [1]. This progressive neurodegenerative disease affects approximately 24 million individuals worldwide, with one new case detected every seven seconds [2]. AD patients exhibit the following symptoms: decline in executive functions, memory impairment, visuospatial and language difficulties, and behavioral disturbances [3].

Using mixed models, we found that a higher mean dose of ChEI, male gender, older age, NSAID/acetylsalicylic acid therapy, and absence of the APOE ε4 allele were predictors of a better short-term ChEI-treatment response and long-term outcome. The type of ChEI did not influence the results. The patients that were more severely impaired cognitively exhibited a better response to ChEI therapy, but declined faster subsequently. Individuals with a lower level of education showed a slower cognitive decline. These findings were similar for both the MMSE and ADAS-cog scales; however, ADAS-cog is more sensitive in detecting effects, which gives credibility to the results. For example, the graded effects of baseline cognitive ability with gender or with age were observed more clearly using the ADAS-cog scale and had larger effect sizes.

In conclusion, this study showed that male gender, older age, absence of the APOE ε4 allele, and NSAID/acetylsalicylic acid treatment or a higher mean dose of ChEI were predictors of better response to ChEI therapy and of a more favorable longitudinal outcome. Lower cognitive ability at baseline was a predictor of improved response to ChEI treatment. The long-term outcome was better for patients with a higher cognitive level at the start of therapy or for less-educated individuals. The demographic and clinical composition of the AD cohort under study may be one of the explanations for the heterogeneity of results observed in different studies. Future studies are warranted to investigate differences in response to treatment and longitudinal outcome based on various patient characteristics. Long-term protective effects, such as the possible impact of NSAIDs or other protective treatments, may take years to develop. The knowledge gained from naturalistic ChEI treatment studies will continue to be important.

AD: Alzheimer’s disease; ADAS-cog: Alzheimer’s Disease Assessment Scale-cognitive subscale; ADL: activities of daily living; APOE: apolipoprotein E; ChEI: cholinesterase inhibitors; CI: confidence interval; DSM-IV: Diagnostic and Statistical Manual of Mental Disorders: 4th edition; IADL: Instrumental Activities of Daily Living Scale; MMSE: Mini-Mental State Examination; NSAIDs: NonSteroidal Anti-Inflammatory Drugs; PSMS: The Physical Self-Maintenance Scale; SATS: Swedish Alzheimer Treatment Study; SD: standard deviation

The authors declare that they have no competing interests.

CW participated in the study, supervised the data collection, was responsible for the statistical design and for carrying out the statistical analyses, interpreted the results, and drafted the paper. AKW and EL participated in the study, assisted in the analysis and interpretation of the data, and critically revised the manuscript. LM designed the study and critically revised the manuscript. All authors read and approved the final manuscript.




0 0 vote
Article Rating
Notify of
Inline Feedbacks
View all comments